Project Summary/Abstract Type 2 diabetes (T2DM) is a major public health concern affecting nearly 30 million people in the U.S. and increasing their risk for serious complications including blindness, amputations, kidney failure, heart attacks and strokes. Forty five percent (45%) of people with diabetes report considerable stress related to their diabetes, which is increasingly being recognized as a key factor in worsening glucose control and the progression of T2DM. The proposed project uses mindfulness-based stress reduction (MBSR), a powerful and well researched mindfulness-based intervention, to address stress as a critical barrier to glucose control in patients with T2DM. The objective of this proposal is to conduct a large, fully-powered randomized controlled trial (RCT) to definitively determine the effects of a 6-month MBSR intervention on glucose control in patients with uncontrolled T2DM. We will randomize 290 adults with uncontrolled T2DM to a 6-month MBSR intervention or health education control. The 6-month intervention will consist of the University of Massachusetts standard 8-week MBSR program followed by monthly MBSR booster sessions. Outcomes will be assessed at baseline, 8-weeks, 6 months and 12 months. Specific Aims are: 1) To conduct a RCT to determine the effects of a 6-month MBSR intervention compared to health education on glucose control in 290 patients with uncontrolled T2DM. The primary outcome will be hemoglobin A1c (HbA1c), a measure of average glucose levels over the past 3 months. We hypothesize that between the two groups, there will be a clinically significant 0.5% absolute difference in the mean change in HbA1c from baseline to month 6. Additionally, we will look at fasting glucose and glucose variability as they are also linked with adverse outcomes; 2) To determine the effects of MBSR versus health education control on psychosocial, behavioral and physiological mechanisms potentially mediating its glucose-lowering effects in patients with uncontrolled T2DM. Subjective stress, diabetes-related distress and other psychosocial measures will be assessed. Accelerometry will be used to track physical activity. Unannounced phone calls will be used to obtain 24 hour diet recalls. Physiologic measures include serum hsCRP and TNF-? as markers of chronic inflammation, salivary cortisol to assess the hypothalamic-pituitary-adrenal axis, and salivary ?-amylase to assess sympathetic nervous system activity. The proposed study has the potential to transform current standards of care for T2DM by using a novel long- term MBSR intervention as a powerful adjunct intervention for T2DM. MBSR could impact the clinical picture of T2DM by empowering patients with skills for strengthening their own internal resources to promote self- regulation and adaptive coping and reduce stress reactivity, which are all essential for implementing healthy behaviors and are expected to lead to improved glucose control and reduced risk of diabetes complications. This proposal is relevant to the mission of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to conduct research on diabetes to improve people's health and quality of life.